Development of a Dynamic Kinetic Resolution for the Isolation of an Intermediate in the Synthesis of Casopitant Mesylate: Application of QbD Principles in the Definition of the Parameter Ranges, Issues in the Scale-Up and Mitigation Strategies

Process development towards the improvement of the manufacturing process of casopitant mesylate (a drug developed by GlaxoSmithKline with activity on the central nervous system) identified a dynamic kinetic resolution opportunity for the improvement of the yield. In this paper, the application of quality by design principles to the DKR is presented together with the issues that were faced during different scale-ups and the at-scale solutions that were implemented.